tbuckley/cabot-search huggingface dataset:
The role of private insurance characteristics in the out-of-pocket costs of patients with multiple myeloma.
Authors: Hamlet Gasoyan, Michael B. Rothberg
Journal: Journal of Clinical Oncology (2023)

6641 Background: Over the past two decades, the major advances in the treatment of multiple myeloma have improved overall survival considerably. High costs of novel medications and patient out-of-pocket costs were suggested to have a role in treatment disparities but available data on total- and patient-out-of-pocket costs are dated. We examined the costs in privately insured patients with newly diagnosed multiple myeloma in the first year after the diagnosis, based on insurance plan characteristics. Methods: This retrospective study used the IBM MarketScan Commercial Database for the years 2011–2019, which consists of medical and prescription medications data from 120+ large employers and 40+ health plans in the US. The primary outcome variables were total- and patient out-of-pocket costs during 1 year after the index diagnosis. Results: 5,487 privately insured adults with an index multiple myeloma diagnosis during 2012-2018 were identified. Approximately 41% (n=2,240) of the study population received bortezomib, 38.6% (n=2,117) received lenalidomide, and 5.7% (n=314) received carfilzomib during 1 year after the index diagnosis. The median total cost of care in the first year after multiple myeloma diagnosis increased from $133,938 (interquartile range, $19,770 – $292,501, expressed in 2018 USD) in patients diagnoses in 2012 to $252,559 ($33,089 – $380,662) in patients diagnoses in 2018. The median patient out-of-pocket costs were $3,147 (interquartile range $1,562 - $5,441, 2018 USD) in patients diagnosed in 2012 and $3,711 ($1,756 – $6,466) in patients diagnosed in 2018. Among patients diagnosed in 2018, the median patient out-of-pocket cost was $1,706 ($902 – $2,873) for patients with low out-of-pocket cost plans, $3,428 ($1,794 – $6,371) for those with average out-of-pocket cost plans, and $5,623 ($3,517 - $7,810) for patients with high out-of-pocket cost plans. Conclusions: While the total cost of care in the first year after multiple myeloma almost doubled during the study period, the patient out-of-pocket costs remained relatively stable. The protections imposed by the Affordable Care Act are likely key in preventing surges in patient out-of-pocket costs. Additional legislative action could help curb the price increases for multiple myeloma medications. [Table: see text]
Impact of surgical treatment on overall survival in cholangiocarcinoma of the gallbladder: An NCDB study.
Authors: Mohammed Al Kurnas, Peter T. Silberstein, Xinxin Wu
Journal: Journal of Clinical Oncology (2023)

e16224 Background: Cholangiocarcinoma (CCA) is a malignancy of the epithelial cells of the biliary tree. Surgical treatment is the preferred treatment option for all subtypes, but 5-year survival rates remain low. The surgical approaches used in the treatment of CCA include radical hepatic resection, laparoscopic, and robotic surgery. Although CCA can arise from the intrahepatic bile duct or extrahepatic bile duct, there exists a subtype with the gallbladder as the primary site. While there have been studies comparing outcomes among surgical procedures, there has yet to be a study that explores the impact of surgery on CCA of the gallbladder. The National Cancer Database (NCDB) was analyzed to determine the effects of surgical modality on overall survival. Methods: A retrospective cohort analysis utilizing the NCDB included 1,880 patients diagnosed with CCA (ICD-8160-3) affecting the gallbladder (topography code C23.9) between 2010 and 2020. Surgical modalities included robotic-assisted, minimally invasive, open, or no surgery. Approaches were categorized by the definitive treatment and open surgeries included procedures converted to open and unspecified. Facility structures were categorized as academic facilities versus non-academic facilities and facility type influence on surgical treatment was compared using Pearson Chi-squared tests. Surgical treatment and facility type on overall survival was analyzed by the Kaplan-Meier method. Results: The majority of the cases analyzed were White (74.7%), female (62.4%), and had Medicare as the primary payor at diagnosis (54.9%). The mean age at diagnosis was 68.4 years (min = 24, max = 90, std. deviation = 11.9) with an average Charlson-Deyo score of 0.5. Of the 1,880 patients analyzed, only 328 underwent surgery (17.4%). There was a statistically significant increase in the overall survival of those who underwent surgery (mean = 33.4 months) over those who did not (mean = 14.7 months, p &lt; 0.001). Those at academic facilities had better overall survival than those at non-academic facilities (p &lt; 0.001), but facility type was not statistically significant for whether patients received surgery. However, those at an academic facility were more likely to have open versus minimally invasive surgery (70.0%) compared to those at a non-academic facility (50.%, p &lt; 0.002). Conclusions: We identified that patients who underwent surgery had significantly better overall survival than those who did not with an average difference of 18.7 months. While there was no difference in the likelihood of having surgery at academic vs. non-academic facilities, the overall survival for those at academic facilities was greater and we found that these patients were more likely to have open surgery over minimally invasive surgery. Further study is needed to determine what other biomedical or socioeconomic factors may account for the difference in overall survival at academic facilities.
The impact of previous local therapy (LT) on overall survival (OS) in patients with advanced hepatocellular carcinoma (aHCC) treated with atezolizumab/bevacizumab (A+B) as first line systemic therapy.
Authors: Maria Elena Fierro, Munaf Alkadimi, Lauren Diaz Boyle, Kana Lucero, Michael Mader, Kathleen Franklin, Zohra Nooruddin
Journal: Journal of Clinical Oncology (2023)

e16129 Background: Treatment options for aHCC have drastically improved over the past few years with immunotherapy at the forefront. Ongoing studies aim to identify the benefit of immunotherapy in combination with local therapies, but there are no studies that analyze the impact of previous local therapy on OS in patients who later receive A+B for treatment of aHCC. This study aims to analyze the impact of previous local therapy on OS in patients with aHCC treated with first line A+B within the Veterans Health Administration (VHA). Methods: Patients with aHCC receiving first line systemic therapy with A+B at VHA between Dec 1, 2019 through Mar 1, 2022 were identified from the electronic medical record (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR and followed the patients from the date of diagnosis, date of local treatment and date of A+ B initiation until death or their last VHA visit with the study period ending on Jan 31, 2023. The Chi-Squared test was used to compare rates and the Mann-Whitney test was used to compare medians. Results: 332 patients with aHCC received A+B. 67% of patients received prior LT. Patients who received LT had better ECOG status, Child-Pugh classification, and BCLC staging at time of diagnosis. There was no difference in age at diagnosis, race/ethnicity, ALBI score at time of diagnosis or at time of starting A+B, or presence of extrahepatic spread at time of starting A+B. There was a statistically significant difference in time from HCC diagnosis to start of A+B, with patients who received LT having a longer interval time. There was a small but not statistically significant difference in median OS from the start of A+B, favoring people who received LT. Conclusions: Our unique retrospective study confirms that patients receiving LT have better OS from the time of diagnosis. Disease biology and LT response may be contributing to this survival benefit. However, the OS was similar from the time of initiation of A+B in patients receiving LT versus patients who did not receive any LT.[Table: see text]
Efficacy of first-line (1L) immunotherapy (IO)-based regimens in patients with sarcomatoid and/or rhabdoid (S/R) metastatic non-clear cell renal cell carcinoma (nccRCC): Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Chris Labaki, Ziad Bakouny, Audreylie Lemelin, Matthew Scott Ernst, Kosuke Takemura, J Connor Wells, Sumanta Kumar Pal, Bernadett Szabados, Benoit Beuselinck, Rana R. McKay, Jae-Lyun Lee, Takeshi Yuasa, Francis Parnis, Georg A. Bjarnason, Bradley Alexander McGregor, David A. Braun, Wanling Xie, Wenxin Xu, Daniel Yick Chin Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2023)

4519 Background: Patients with advanced RCC with S/R components exhibit poor clinical outcomes. IO-based combination therapies demonstrated substantial efficacy among patients with metastatic S/R ccRCC, compared to VEGF targeted therapy (VEGF-TT). Recent trials showed promising activity of IO-based regimens in patients with advanced nccRCC. We sought to assess the efficacy of IO regimens among patients with S/R nccRCC. Methods: Patients with advanced nccRCC treated with 1L IO regimens (IO/IO or IO/VEGF-TT) or 1L VEGF-TT monotherapy (sunitinib or pazopanib) were included. Cases were categorized as S/R or non-S/R. The primary outcomes were overall survival (OS) and time to treatment failure (TTF) in patients with S/R nccRCC receiving 1L IO or VEGF-TT. Overall response rate (ORR) was a secondary outcome. OS and TTF were compared between groups (IO vs. VEGF-TT) using Cox regression models adjusted for age, IMDC risk groups, and nccRCC subtype. ORR was compared between groups (IO vs. VEGF-TT) using a logistic regression adjusted for the same confounders. Results: Overall, 103 patients with S/R nccRCC were included, of whom 33 (32%) received 1L IO regimens. Median follow-up was 31 months. After adjustment for confounding factors, patients with S/R nccRCC treated with IO regimens presented with significantly improved survival outcomes as compared to those receiving VEGF-TT (median OS [mOS]: NR vs. 7.1 and mTTF: 9.4 vs. 2.9 mos for IO regimens and VEGF-TT, respectively). Similarly, a higher ORR was seen in patients with S/R nccRCC receiving IO regimens versus VEGF-TT (34.1 vs. 10.9%, respectively). Among 430 patients with non-S/R nccRCC (IO regimens: n=44), no significant differences in survival outcomes between regimen classes were seen (mOS: 24.4 vs. 14.8 and mTTF: 4.2 vs. 5.0 mos for IO regimens and VEGF-TT, respectively). Conclusions: To our knowledge, this represents the largest effort to characterize the outcomes of patients with S/R nccRCC treated with IO regimens. Patients with S/R nccRCC appear to derive a substantial and selective benefit from IO regimens (vs. VEGF-TT). These data support the use of IO-based regimens in patients with S/R nccRCC. [Table: see text]
Prospective evaluation of the utility of concurrent 18F-FDG PET/CT and 68Ga-DOTA-TOC imaging in gastroenteropancreatic neuroendocrine neoplasms (GEPNENs): The PETNET study.
Authors: Joao Paulo Solar Vasconcelos, Marilyn Zhou, Pavithraa Ravi, Hayley Allan, Heather Saprunoff, Ingrid Bloise, Sara Harsini, Don Wilson, Francois Benard, Patrick Martineau, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2023)

4022 Background: Somatostatin receptor imaging (SRI) is a standard of care for patients with GEPNETs. The additional value of concurrent 18F-FDG PET/CT (FDG PET) remains unclear. We reviewed a prospective functional imaging study to determine the utility of FDG PET in GEPNENs. Methods: PETNET is a prospective study in British Columbia, Canada, which provides all 68Ga-DOTA-TOC (DOTA PET) imaging in the province. Every patient receives a DOTA PET scan and an FDG PET within 30 days. PETNET enrolls all patients with an indication for SRI. Scans are ordered per treating physician discretion at any point in the disease course. This abstract focuses on the WD-GEPNEN population. Only the first dual functional imaging scans were analyzed and FDG was interpreted qualitatively (positive/negative). Results: From 04/2017-01/2023, 375 patients with NEN were enrolled, 165 (44%) with metastatic GEPNENs. Baseline characteristics are described. Median time between scans was 4 days (IQR 1-11). The proportion of patients with positive FDG PET at baseline increased with WHO grade. For patients with well differentiated G1 to G3 GEPNENs (N=161), overall survival was significantly lower with a positive FDG PET (HR: 4.22; 95%CI 1.61-11.02 p=0.001). FDG remained prognostic when G3 tumors were excluded (N=148) (HR 3.52; 95%CI 1.32-9.42 p= 0.007). When analyzing dual tracer PET imaging, patients with DOTA+/FDG- had reduced risk of dying in comparison with DOTA+/FDG+ (HR:0.26; 95%CI 0.09-0.67 p=0.01). After multivariate analysis, FDG positivity remained independently associated with reduced survival (HR 2.87; 95%CI 1.06-7.75 p=0.04) when controlling for grade of tumor and age. Conclusions: In this prospective cohort of metastatic GEPNENs, a positive FDG PET was significantly associated with reduced overall survival. These results provide additional evidence to support dual tracer functional imaging use in metastatic well differentiated GEPNEN’s. [Table: see text]
Biomarker subpanel customization for different use cases in acute myeloid leukemia research.
Authors: Wenjun Li, Shaoheng Liang, Hannah Roberts, Long Dao, Yalei Wu, David Zhang, Alessandro Pinto
Journal: Journal of Clinical Oncology (2023)

e19026 Background: Treatment guidance and decision making according to modified RECIST guidelines often depends on characterization of these biomarkers in patients with cancer. Although panels with larger breadths of coverage are useful for initial detection of these biomarkers for evaluation of disease burden and prognosis, their cost-effectiveness decreases as treatment and disease progress; smaller subpanels may yield equally valuable information into disease progress and guide treatment in a more cost-effective manner, potentially leading to more datapoints in decision making in comparison to larger panels. Methods: QBDA is an NGS enrichment research technology that allows the enrichment of rare variants, reducing the sequencing cost while maximizing the sensitivity. Here we introduce a new capability of our platform that allows tailoring sequencing panel breath to the disease stage needs. We demonstrate the ability to generate a 384-plex NGS subpanel from a 2400-plex acute myeloid-leukemia (AML) measurable residual disease (MRD) targeting research panel. Both panels were tested on both wild-type and 0.1% variant allele frequency (VAF) AML MRD contrived samples. Results: Without any optimization of the subpanel itself, the subpanel exhibited similar or better performance to the main panel. The main panel had a ~80% uniformity of coverage whereas the subpanel had a uniformity of coverage exceeding 75%. The subpanel covers fewer genes of interest and requires fewer overall reads. Both panels had a bulk LoD of below 0.1% VAF. Conclusions: This data represents proof-of-concept for the design of small custom panels from large-scale multiplex panels for different use cases, potentially increasing cost-effectiveness.
Hearing loss related outcomes post-lateral temporal bone resection and other oncologic treatment.
Authors: Shirin Jivani, Kate A. Hutcheson, Marc-Elie Nader, Rajarshi Pratihar, Claudia Karina White, Paul Gidley
Journal: Journal of Clinical Oncology (2023)

e18069 Background: Lateral temporal bone resection (LTBR) is used to treat malignancies originating from the auricle, periauricular skin, external auditory canal, parotid gland, or temporal bone. LTBR is the workhorse of otologic cancer surgery; however, few studies have described audiologic outcomes in a large sample of patients. The current literature focuses on overall survival rates post-surgery; however, hearing loss-related outcomes after surgery and adjuvant therapy are lacking in the literature. Following surgery, patients are expected to have maximal conductive hearing loss in the affected ear which can be augmented by ototoxic effects of adjuvant treatment such as radiation and systemic therapy. This type of hearing loss significantly impacts quality of life, making it difficult to understand speech directed to the surgically closed ear, localize sounds, and understand conversational speech in noisy environments. Less is known about the rate and severity of sensorineural hearing loss (SNHL) following LTBR. Methods: A retrospective chart review was conducted among 252 patients who underwent LTBR at single tertiary care center from 2010 to 2020. We evaluated changes in ipsilateral bone conduction (BC) hearing thresholds after LTBR ± adjuvant therapy, including head and neck radiation, chemotherapy, and immunotherapy. Patients who completed at least 1 preoperative and 1 postoperative audiogram within 2 years of surgery were included. Patients who had preoperative chemotherapy, immunotherapy, or temporal bone radiation were excluded. Of 252 patients reviewed, 94 met the eligibility criteria. Audiometric data included pure tone average (PTA) for BC thresholds. A significant decline in hearing was defined as an increase in PTA ≥ 10 decibels (American Academy of Otolaryngology-Head and Neck Surgery). Three treatment subgroups were analyzed, including LTBR only, LTBR and radiation therapy, and LTBR with radiation and systemic therapy. Results: Among all patients, BC PTA increased on average by 7dB after treatment (p&lt;0.001); 30% of patients had ≥ 10dB shift. Patients undergoing LTBR with adjuvant therapy had a higher rate of hearing loss compared to patients undergoing LTBR alone (22/69, 32% vs. 5/25, 20%, respectively). Conclusions: LTBR can cause significant long-term decline in BC hearing that is worsened with the addition of adjuvant therapy. Therefore, it is critical to systematically obtain preoperative and post-treatment audiologic testing to monitor and rehabilitate hearing loss over time. The findings of this study may help patients understand realistic expectations of long-term treatment outcomes related to hearing loss, as an initial step to help improve quality of life with hearing rehabilitation such as osseointegrated bone conduction devices.
Effect of MDSC-targeted TFF2-MSA with PD-1 blockade therapy in advanced gastric cancer models.
Authors: Jin Qian, Sandra Ryeom, Bruce L Daugherty, Seth M. Lederman, Timothy C. Wang
Journal: Journal of Clinical Oncology (2023)

e16037 Background: Recent studies revealed chemotherapy increases anti-PD1 response of gastric cancer (GC) by reducing myeloid-derived suppressor cells (MDSCs). However, a more specific MDSC-targeted treatment is needed to further improve anti-PD1 efficacy in advanced GC. Trefoil factor family 2 (TFF2), a partial agonist of CXCR4 and a secreted anti-inflammatory peptide, can suppress MDSC expansion. Here, we developed a novel MDSC-targeted peptide TFF2-MSA and investigated whether it can synergize with anti-PD1 in syngeneic GC mouse models. Methods: Murine serum albumin (MSA) was fused to murine TFF2 to generate TFF2-MSA peptide with an extended serum half-life. ACKP (Atp4b-Cre; Cdh1-/-; LSL-KrasG12D; Trp53-/-) GC cells developed from a highly malignant diffuse GC mouse model were grafted subcutaneously into HDC-GFP transgenic mice in which the immunosuppressive histidine decarboxylase (HDC)-expressing myeloid cells were traced with GFP. These recipient mice then received either TFF2-MSA or anti-PD-1 antibody or both when tumors reached 150 mm 3 . At the endpoint, flow cytometry analysis was performed to examine immune profiles. In parallel, a group of the s.c. tumor bearing mice were followed up for survival differences in response to the treatments. In the orthotopic model, ACKP-luc cells were implanted to stomach submucosa, and recipient mice received the same treatments started after 1 week. In the metastasis model, subcutaneous flank tumors were resected in ACKP-grafted mice once tumors reached 500 mm 3 to permit spontaneous lung metastasis, and mice then received the same treatments. Results: While either TFF2-MSA or PD-1 antibody showed little benefit as a single agent (TGI 15% and 25% respectively, p&gt;0.05), their combination dramatically suppressed ACKP s.c. tumor growth (TGI 78%, p&lt;0.0001) and markedly prolonged median survival (64 days vs. 32.5 days in control) in a synergistic manner. The combination therapy efficiently reduced tumor HDC-GFP + MDSCs by 67%, and profoundly increased tumor-infiltrating cytotoxic CD8 + T cells by 18 fold. The myeloid/lymphoid progenitor and output ratio in the bone marrow were decreased by the combination, to a similar level of tumor-free mice. While standard chemotherapy (5-fluorouracil and oxaliplatin) showed no efficacy, adding chemotherapy to the combination further improved treatment efficacy (TGI 91%) and extended median survival to 73 days. In addition, in the orthotopic model, the TFF2-MSA/PD-1 antibody combination eradicated GC in 80% mice without recurrence compared to 0% with either monotherapy. Finally, the combination of TFF2-MSA/PD-1 antibody significantly reduced 80% lung metastasis (vs. control, p&lt;0.0001), compared to minimal inhibition with either monotherapy (p&gt;0.05). Conclusions: Targeting MDSCs using TFF2-MSA synergizes with PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of gastric cancer.